US7081132B2 - Flexible barb for anchoring a prosthesis - Google Patents
Flexible barb for anchoring a prosthesis Download PDFInfo
- Publication number
- US7081132B2 US7081132B2 US10/431,809 US43180903A US7081132B2 US 7081132 B2 US7081132 B2 US 7081132B2 US 43180903 A US43180903 A US 43180903A US 7081132 B2 US7081132 B2 US 7081132B2
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- Prior art keywords
- barb
- prosthesis
- union
- strut
- point
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/848—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents having means for fixation to the vessel wall, e.g. barbs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/848—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents having means for fixation to the vessel wall, e.g. barbs
- A61F2002/8483—Barbs
Definitions
- This invention relates to medical devices, more particularly to stents and other prosthetic devices having anchoring barbs.
- Migration can be a significant problem in the placement of expandable stents and other intraluminal devices, particularly when placed in the vascular system where the prosthesis is subject to the forces of blood flow, especially on the arterial side. Nowhere is the prevention of migration more important and more challenging than when placing a stent graft to repair an abdominal aortic aneursym (AAA) where downstream migration of the device can result in the aneursym no longer being excluded. If the aneurysm is no longer intact or subsequent rupture were to occur, the patient would then face an increased risk of death. Unlike surgically placed grafts which are sutured into place, only the radial forces of the stent would be available to hold the prosthesis into place.
- AAA abdominal aortic aneursym
- stent graft manufacturers sometimes place a series of barbs or hooks that extend outward from the main body of the prosthesis, typically at its proximal end, either by attaching them to the stent frame with solder or by some other bonding technique, or to the graft material, typically by suturing. It has been observed that sutures attaching barbed stents to the graft material are subject to breakage due in part to the flexibility of the graft material and the considerable pulsatile forces of arterial blood acting on the device. These forces have been known to directly contribute to the detachment between the graft portion and anchoring stent.
- barbs soldered or otherwise attached to the stent frame are subject to fracture, detachment, or other failure, especially when the forces become concentrated at a particular location along the stent graft.
- simply making the barbs stronger to prevent fracture can result in increased damage to the anchoring tissue.
- adding rigidity to any outward-projecting barbs may compromise the ability of the device to be compressed and loaded into a delivery system.
- the use of multiple barbs can prevent catastrophic migration of the device, especially if there are a very limited number of barb failures.
- a single barb failure should not result in the migration of the device and may not represent a problem clinically, barb fracture or failure is nevertheless currently classified as an adverse event that manufacturers seek to avoid.
- an illustrative barbed prosthesis such as a stent or stent graft
- the barb 11 comprises a basal portion that joins the strut of the prosthesis from which the barb extends, and a stress-dispersing region located between the anchoring portion and the basal portion, usually closely adjacent to the basal portion, that is adapted to better distribute stresses and strain caused by forces acting on the barb, thus preventing their concentration at a particular point which would increase the likelihood of barb fracture.
- a ‘barb’ is defined as an elongate or short structure such as a straight or curvilinear wire, hook, projection, etc., typically including a distal end that includes a sharp edge and/or point, that extends outward from some portion of the prosthesis and is designed to penetrate tissue adjacent to the prosthesis, such as the walls of a vessel, to temporarily or permanently anchor the device at the location of deployment within the body of a patient.
- the barb can comprise the same material as the prosthesis, such as stainless steel, a superelastic alloy, polymer, etc., or of a different material.
- the barb may be attached to the prosthesis mechanically, such as being wound or crimped; bonded, such as by solder, an adhesive, or welding; fastened in a manner to allow it to slide along the strut (typically until contacting a stop); or the barb may represent an integral part of the prosthesis. It may be advantageous in particular applications to form the stress-dispersing region in a manner to prevent significant residual stresses in the material. This can be accomplished by the use of methods or materials well known the art.
- the basal portion and stress-dispersing region comprises a helical coil that is wound around the barb to which it is attached.
- the windings of the basal portion form a mechanical attachment to which a solder joint or other bonding means is added as a second means of attachment.
- the present invention may include either means of fixation or attachment of the barb to the strut (or neither in the case of an integral barb) and does not require that both types of fixation be present.
- One advantage of the mechanical fixation is to provide a backup means of fixation in the event that the solder erodes from contact with bodily fluids.
- the last or distal winding of the helical coil comprises the stress-dispersing region and is typically of a greater pitch than the windings of the basal portion. It also does not include solder or some other bonding means that affixes it to the strut of the prosthesis, nor does it generally contact the strut. This allows the last winding to remain flexible and thus, accommodate the forces acting upon the anchoring portion of the barb, which is embedded in the adjacent tissue.
- the second end of the barb can comprise a second anchoring portion and stress-dispersing region extending oppositely from the basal portion and area of fixation to form a double-ended barb.
- the basal portion of the strut is secured to the strut with a piece of cannula or similar structure that is crimped or bonded in place, such as with the illustrative solder joint.
- the stress-dispersing region comprises a pair of bends that facilitate lateral flexing of the barb to reduce the risk of fracture.
- the barb extends from the solder joint, then assumes a series of stress-dispersing bends that are proximal to the anchoring portion.
- the stress-dispersing region of the barb comprises a coiled loop bend, U-shaped bend, or other series of bends distal to the point of attachment to add flexibility to the barb, thus reducing bending fatigue and the risk of barb fracture.
- the barb may include both a coiled loop bend (or other type of bend) and a free helical winding to add further flexibility.
- the barb integrally formed with the strut such as by laser cutting a flat sheet or cannula.
- the stress-dispersing area comprises one or more bends and/or fillets to prevent the concentration of stress in the area immediately adjacent the union between the strut and barb.
- FIG. 1 depicts a side view of a prior art barb soldered to the strut of a stent
- FIG. 2 depicts a side view of the illustrative embodiment of the present stent barb having a stress-dispersing region
- FIG. 3 depicts a side view of the barb of FIG. 2 prior to attachment to the strut;
- FIG. 4 depicts a side view of an embodiment of the present invention in which the barb is attached to the strut using a piece of cannula;
- FIGS. 5–5 b each depict a side view of an embodiment of the present invention in which the stress-dispersing region of the barb includes a coiled bend;
- FIG. 6 depicts a side view of an embodiment of the present invention in which the stress-dispersing region of the barb comprises a complex bend
- FIG. 7 depicts a side view of an embodiment of the present invention in which the barb in integral with the strut of the stent.
- FIG. 8 depicts a side view of an embodiment of the present invention in which the barb includes more than one anchoring portion and associated stress-dispersing region.
- FIGS. 2–8 depict a medical prosthesis 10 , such as a stent, stent graft, valve, vessel occluder, filter, or other intraluminal medical device, that includes one or more barbs 11 that comprise an anchoring portion 12 sized and oriented to engage tissue for the purpose of anchoring the device and preventing the downstream migration thereof; a basal portion 13 located about the physical union between the barb and the strut of the prosthesis 10 to which it is affixed; and a stress-dispersing region that forms a transition between the basal portion 13 and anchoring portion 12 of the barb 11 .
- a medical prosthesis 10 such as a stent, stent graft, valve, vessel occluder, filter, or other intraluminal medical device, that includes one or more barbs 11 that comprise an anchoring portion 12 sized and oriented to engage tissue for the purpose of anchoring the device and preventing the downstream migration thereof; a basal portion 13 located about the physical union between the barb and the strut of the prosthesis
- the stress-dispersing (or stress-reducing) region 14 of the present invention comprises a section of the barb that has been shaped and configured to receive most of the forces acting upon the anchoring portion 12 or moment arm of the barb as it bends and distribute them throughout that region 14 , rather than allowing them to be concentrated at a single point or relatively narrow region, such as the point of union 19 between the barb 11 and substrate of origin 15 , the substrate of origin 15 typically being a strut 15 of a intraluminal stent or other prosthesis to which the barb 11 is attached.
- strut 15 may encompass a wire, bar, bend, or any portion of the prosthesis from which the barb may emanate, and is not necessarily limited to a strut as traditionally defined in the medical arts, typically meaning a thin section of the metal framework of a self-expanding or balloon expandable stent.
- the barb may be sewn or otherwise attached directly to graft material or another portion of the prosthesis, or it may be formed integrally with the prosthesis.
- the barb may be slidably affixed to the strut 15 to at least temporarily help relieve stresses about the point of union 19 , which is generally defined as that point where the barb extends away from the substrate of origin 15 and/or the means of mechanical attachment 17 or bond 18 between the two.
- the basal portion may represent a well-defined and distinct section of the barb, or merely represent the point of attachment or union with the strut 15 or framework of the prosthesis 10 .
- the stress-dispersing region 14 may extend sufficiently away from the strut 15 that it also may penetrate adjacent tissue and serve to help anchor the stent. Generally, however, the stress-dispersing region 14 is located proximate to the point of union 19 such that the anchoring portion 12 provides most of the anchoring function.
- the addition of structure for reducing moment of stress can be placed anywhere along the length of the barb 11 , it is most advantageous when located near the base thereof (point of union 19 ), especially if the stress load is being placed over a significant portion of the barb's length.
- a series of bends or coils located exclusively at the midpoint of the barb 12 would provide little, if any, stress-relieving value if those bends become imbedded in tissue. In such a situation, the stress moment caused by the torsional and other bending forces acting on the barb would be transferred down toward the barb's base where stress-dispersing structure is lacking.
- FIGS. 2 and 3 depict an illustrative embodiment of the present invention of a type of barb 11 that includes a helical coil 38 that is wound around the strut 15 to which it is attached.
- the barb 11 in configured to anchor a stent or other prosthesis, such as the suprarenal stent of a endovascular stent graft, such as a ZENITHTM AAA Endovascular Graft (Cook Incorporated) used to treat an abdominal aortic aneurysm (AAA) located in the vicinity of the aortic bifurcation.
- a stent or other prosthesis such as the suprarenal stent of a endovascular stent graft, such as a ZENITHTM AAA Endovascular Graft (Cook Incorporated) used to treat an abdominal aortic aneurysm (AAA) located in the vicinity of the aortic bifurcation.
- AAA abdominal aortic aneurysm
- a series of staggered barbs are affixed to the proximal, suprarenal Z-STENTTM (Cook Inc.) to anchor the stent graft within the proximal neck of the aneurysm being treated and prevent downstream migration of the device which could lead to leakage of blood into the aneurysmal sac.
- the illustrative barb 11 is designed to orient away from the heart in the direction of aortic blood flow; however, oppositely-oriented barbs may be used in certain other devices intended for aneurysm repair, such as a thoracic stent graft which would be placed in the aortic arch.
- the orientation of the barb in each of the embodiments of the present invention is determined not only by where the device is placed in the body (i.e., accounting for the direction of blood or fluid flow), but by the type of barb as well, e.g., whether or not the barb includes a hooked end 29 , as depicted in FIG. 8 .
- barbs of different orientation may be used within the same device.
- a length of 0.008–0.012′′ diameter wire (such as 0.01′′ spring stainless steel wire) is either machine wound or hand wound around the strut 15 such that the strut traverses the lumen 21 formed by the helical coil 38 , thus forming a mechanical attachment 17 between the barb 11 and strut 15 , best shown in FIG. 3 .
- the helical windings 16 of the basal portion 13 have a first pitch 31 in which the windings 16 typically, but not necessarily, lie directly adjacent to one another.
- low-temperature silver solder or some other bonding agent, is applied to the windings 16 of the basal portion 13 to form a permanent bond 18 that reinforces the mechanical attachment of the helical windings and secures the barb longitudinally along the strut 15 .
- alternative methods of forming a permanent bond 18 include welding or the use of adhesives.
- helical coil 38 includes a winding 20 distal to those of the basal portion 13 and the point of union 19 between the barb 11 and strut.
- the free winding 20 because it neither is soldered to the strut, or is generally in contact with the strut, except perhaps in an insignificant or incidental way, the free winding comprises the stress-dispersing region 14 of the barb. It should be noted that the free winding 20 does not necessarily completely encircle the substrate of origin or strut and may only constitute a partial winding.
- the free winding 20 is of a second pitch 32 that is typically greater (more loosely wound) than the first pitch 31 of windings 16 of the basal portion 13 , although it is not essential that the basal winding 16 be closely adjacent to one another as depicted.
- the bending stress is more evenly distributed than would be the case if there were a tighter winding (with less pitch), thereby increasing the fatigue life of the barb.
- the fact that the free winding 20 of the barb is not affixed to, nor is in contact with, the strut 15 allows the entire free winding 20 to freely flex and distribute most the bending forces over its entire length. This helps prevent the concentration of torsional and bending stresses at the point of union 19 where the barb 11 extends out from the solder joint 18 , typically the most common location of barb fracture in the prior art barb illustrated in FIG. 1 .
- the anchoring portion 12 of the illustrative barb 11 of FIG. 2 comprises a straight section extending from the stress-dispersing portion such that the overall barb 11 length is about 5 mm, the typical range being 3–8 mm, depending on the stent used.
- the barb 11 extends at an angle 33 from the strut to facilitate the capture of anchoring tissue, the preferred post-deployment angle 33 being about 20–50°, e.g. 35°, in the illustrative embodiment used to anchor the suprarenal stent of a AAA endovascular graft. Due to plastic deformation that may occur during loading of the device into a delivery system, such as a top cap, this angle may be initially formed at a somewhat larger angle 33 (i.e., 40–80°).
- the distal end 30 of the barb includes a bevel 35 to facilitate penetration of the vessel wall, with the sharp point being oriented toward the strut 15 .
- the particular barb angle 33 and bevel 35 orientation are selected, in part, to ensure that the device 10 can be compressed to a smaller configuration and loaded into the top cap (not shown) of a delivery system and successful deployed therefrom such that the barb 11 does not deform or become caught within the cap, while still being able to resiliently extend outward to its expanded configuration and effectively engage tissue.
- FIG. 4 depicts an alternative embodiment of the present invention in which a short piece of metal cannula 22 is used as the mechanical attachment 17 to affix the barb 11 to the strut 15 of the intraluminal prosthesis 10 .
- the basal section 13 of the barb 11 is secured against the strut 15 by the cannula 22 , which is crimped over the barb and/or affixed using a solder joint 18 or some other means of fixation.
- the barb 11 assumes a series of bends or curves 24 that comprise the stress-dispersing region 14 , after which the anchoring portion 12 extends outward at the appropriate angle from the strut 15 .
- the cannula 22 can be used in combination with another type of mechanical attachment 17 , such as the helical windings 16 of FIG. 3 in which the last winding 20 would comprise the stress-dispersing region 14 .
- FIGS. 5–6 depict alternative embodiments of stress-dispersing regions 14 of the barb 11 of the present invention which can be used with a variety of basal portion 13 configurations and types of attachments 17 .
- stress-dispersing region 14 comprises a complete coiled loop 23 whereby the wire makes approximately a one and quarter turn between the basal portion 13 the anchoring portion 12 of the barb 11 .
- the illustrative loop 23 provides a known mechanical advantage that it increases the range of flexibility at that bend, as evidenced by its use in certain medical devices, such as stents, and other devices with sharp bends (e.g., safety pins).
- FIGS. 5 a and 5 b depict embodiments that include both the free winding 20 as depicted in the embodiments of FIGS. 2–3 , as well as a coiled loop 23 that is located adjacent to the free winding 20 .
- the coil is discrete from the free winding 20 , wherein in the embodiment of FIG. 5 b, a portion of the coiled loop 23 originates from the free winding 20 such that they are essentially contiguous with one another.
- the combination of the coiled loop 23 and free winding 20 form a stress-dispersing region 14 having different flexibility characteristics that may be desirous in a particular application.
- the embodiment of FIG. 6 includes a generally U-shaped bend 24 that comprises the stress-dispersing region 14 .
- the embodiments of FIGS. 5–6 are merely exemplary of the numerous configurations of bends 24 that can be utilized to redistribute bending stresses and reduce the risk of fracture. These and other undisclosed bends may used in combination within the stress-dispersing region 14 to further distribute the stress load of the implanted barb 11 .
- the bends 24 may be combined with a free helical winding 20 for added flexibility.
- FIG. 7 depicts an integrally formed barb 11 in which the barbed prosthesis 10 is partially or completely formed from a sheet of metal or other material, such as by laser cutting, eliminating the need for an separate attachment mechanism 17 .
- the basal section 13 of the barb 11 basically comprises the point of union 19 between the strut portion 15 and the barb portion 11 from which it extends.
- the stress-dispersing region 14 comprises a series of bends 24 , as well as a fillet 25 at the union 19 with the strut to further reduce stress concentration.
- FIG. 8 depicts an embodiment of the present invention in which the prosthesis 10 includes a doubled-ended barb 11 having a first barb portion 36 that includes a first anchoring portion 12 and associated first stress-dispersing portion 14 , and a second barb portion 37 that includes a second anchoring portion 26 and associated second stress-dispersing portion 27 , all extending from a single basal portion 13 , which in the illustrative embodiment, comprises a helical coil 38 similar to that depicted in FIG. 3 .
- Both the first free winding 20 extending from the first barb portion 36 and the second free winding 27 extending oppositely from the basal portion 13 are unattached to the strut 15 and free to flex and distribute any bending stresses therealong. Additionally, FIG.
- the exemplary double-ended barb 11 can be modified to include other disclosed configurations of the basal, stress-dispersing or anchoring portions or regions 12 , 13 , 14 of the barb 11 or any appropriate means of attachment to the strut 15 .
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
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Abstract
Description
Claims (20)
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/431,809 US7081132B2 (en) | 2002-05-16 | 2003-05-08 | Flexible barb for anchoring a prosthesis |
US10/642,513 US20040117004A1 (en) | 2002-05-16 | 2003-08-15 | Stent and method of forming a stent with integral barbs |
US11/849,858 US7828839B2 (en) | 2002-05-16 | 2007-09-04 | Flexible barb for anchoring a prosthesis |
US13/471,066 US20120222969A1 (en) | 2002-05-16 | 2012-05-14 | Stent and method of forming a stent with integral barbs |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US38104602P | 2002-05-16 | 2002-05-16 | |
US10/431,809 US7081132B2 (en) | 2002-05-16 | 2003-05-08 | Flexible barb for anchoring a prosthesis |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/642,513 Continuation-In-Part US20040117004A1 (en) | 2002-05-16 | 2003-08-15 | Stent and method of forming a stent with integral barbs |
Publications (2)
Publication Number | Publication Date |
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US20030236570A1 US20030236570A1 (en) | 2003-12-25 |
US7081132B2 true US7081132B2 (en) | 2006-07-25 |
Family
ID=29550059
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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US10/431,809 Expired - Lifetime US7081132B2 (en) | 2002-05-16 | 2003-05-08 | Flexible barb for anchoring a prosthesis |
Country Status (6)
Country | Link |
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US (1) | US7081132B2 (en) |
EP (1) | EP1503702B1 (en) |
JP (1) | JP4624779B2 (en) |
AU (1) | AU2003243204B2 (en) |
DE (1) | DE60334791D1 (en) |
WO (1) | WO2003096935A1 (en) |
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US20040220682A1 (en) * | 2003-03-28 | 2004-11-04 | Gi Dynamics, Inc. | Anti-obesity devices |
US20050060018A1 (en) * | 2003-09-16 | 2005-03-17 | Cook Incorporated | Prosthesis deployment system |
US20050075622A1 (en) * | 2002-12-02 | 2005-04-07 | Gi Dynamics, Inc. | Bariatric sleeve |
US20050125075A1 (en) * | 2003-12-09 | 2005-06-09 | Gi Dynamics, Inc. | Intestinal sleeve |
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US20080033534A1 (en) * | 2002-05-16 | 2008-02-07 | Cook Incorporated | Flexible Barb for Anchoring a Prosthesis |
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US20110098825A1 (en) * | 2009-10-27 | 2011-04-28 | Kyong-Min Shin | Stent for prostatic urethra expansion |
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US8092521B2 (en) | 2005-10-28 | 2012-01-10 | Jenavalve Technology, Inc. | Device for the implantation and fixation of prosthetic valves |
US8206437B2 (en) | 2001-08-03 | 2012-06-26 | Philipp Bonhoeffer | Implant implantation unit and procedure for implanting the unit |
US8226701B2 (en) | 2007-09-26 | 2012-07-24 | Trivascular, Inc. | Stent and delivery system for deployment thereof |
US8241346B2 (en) | 2001-12-20 | 2012-08-14 | Trivascular, Inc. | Endovascular graft and method of delivery |
US8317858B2 (en) | 2008-02-26 | 2012-11-27 | Jenavalve Technology, Inc. | Stent for the positioning and anchoring of a valvular prosthesis in an implantation site in the heart of a patient |
US8328861B2 (en) | 2007-11-16 | 2012-12-11 | Trivascular, Inc. | Delivery system and method for bifurcated graft |
US8398704B2 (en) | 2008-02-26 | 2013-03-19 | Jenavalve Technology, Inc. | Stent for the positioning and anchoring of a valvular prosthesis in an implantation site in the heart of a patient |
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AU2003243204A1 (en) | 2003-12-02 |
WO2003096935A1 (en) | 2003-11-27 |
AU2003243204B2 (en) | 2008-09-18 |
EP1503702B1 (en) | 2010-11-03 |
US20030236570A1 (en) | 2003-12-25 |
JP2005525871A (en) | 2005-09-02 |
EP1503702A1 (en) | 2005-02-09 |
DE60334791D1 (en) | 2010-12-16 |
JP4624779B2 (en) | 2011-02-02 |
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